Nobuhiko Suganuma

Uterine autotransplantation in cynomolgus macaques: the first case of pregnancy and delivery

BACKGROUND For women with congenital uterine infertility, or for those who have undergone hysterectomy, uterine transplantation is one of the potential treatments to regain fertility. In this study, we utilized a primate model of uterine transplantation, and evaluated the patency of our microsurgical anastomoses, and the perfusion of the transplanted uterus. METHODS Two female cynomolgus monkeys underwent surgery. We anastomosed two arteries and one vein in Case 1 and two arteries and two veins in Case 2. The arteries used were the uterine arteries and the anastomosis was done to the external iliac artery. We used one of the ovarian veins in both animals, but resected the ovary from the Fallopian tube. Uterine arterial blood flow and uterine size were determined by intraoperative indocyanine green (ICG) angiography and ultrasonography. The biopsy of the uterine cervix was performed after surgery. RESULTS ICG angiography showed that the unilateral uterine artery perfused the bilateral uterine bodies and cervix. In Case 1, ICG angiography showed the occlusion of one of the anastomosed arteries during the operation and the uterus appeared atrophied 2 months after operation. In Case 2, the transplanted uterus survived and normal menstruation occurred. The animal achieved a natural pregnancy and was delivered by the Caeserean section due to early separation of the placenta. The newborn suffered fetal distress. CONCLUSIONS These results show the anastomosis of at least the bilateral uterine arteries and the unilateral ovarian vein is required for uterus transplantation. This is the first report of a natural pregnancy in a primate following uterine autotransplantation.

Uterus autotransplantation in cynomolgus macaques: intraoperative evaluation of uterine blood flow using indocyanine green

BACKGROUND Uterus transplantation may be the only theoretical option for some women, for example, those with congenital uterine infertility or who have undergone hysterectomy. In this study, we evaluated the intra- and post-operative blood flow conditions of vascular anastomosed regions and the blood-perfused area of the transplanted uterus in a cynomolgus macaque model of uterus autotransplantation. METHODS Female cynomolgus monkeys (n = 6) underwent surgery: the first two animals were used to study the pelvic vascular anatomy and the remaining four animals were used for uterus autotransplantation. We used indocyanine green (ICG) fluorescent angiography during surgery to assess blood perfusion in the vascular anastomosed region and uterine area. After surgery, the uterine size, presence or absence of the endometrium and blood flow rates in the uterine artery and vein were evaluated using Doppler ultrasonography. RESULTS; Uterine arterial and venous anastomoses succeeded in all four animals that underwent autotransplantation. Intraoperative ICG fluorescence angiography showed favorable blood flow in the vascular anastomosed regions and the entire uterus received a sufficient blood supply from a single uterine artery. Favorable blood flow in the uterine artery and vein immediately after surgery was shown by Doppler ultrasonography. Ultimately, three out of four animals died within 3 months following surgery because of reduced feeding and loss of body strength. CONCLUSIONS ICG fluorescence angiography can be used for simple evaluation of real-time blood flow conditions in the anastomosed uterine artery, vein and uterine area and can facilitate the success rate of uterus transplantation.

Quality of life evaluation in Japanese pregnant women with striae gravidarum: A cross-sectional study

BackgroundStriae gravidarum is a physiological skin change that many pregnant women experience during pregnancy. The striae are often accompanied by a reddish purple color during pregnancy, and then lose pigmentation and become atrophic in the long term after pregnancy. Striae gravidarum seems to be undesirable to many pregnant women. However, the impact of striae gravidarum on pregnant women who experience it has not been clarified. The aim of this study was to evaluate the impact of striae gravidarum on the generic and dermatology-specific quality of life (QOL) of pregnant women.MethodsA cross-sectional study was conducted at three private clinics in a typical urban area in Japan. We recruited 447 pregnant women at 36 weeks of gestation; One hundred and ninety-nine pregnant women at 36 weeks of gestation participated in the study and 179, consisting of 94 primiparae and 85 multiparae, were analyzed.We used and assessed Davey’s score for striae gravidarum, World Health Organization Quality of Life assessment questionnaire for generic QOL, and Skindex-29 for dermatology-specific QOL.ResultsThe prevalence of striae gravidarum was 39.1% (27.7% in primiparae, and 51.8% in multiparae). Although there were no differences in generic QOL scores between the presence and absence of striae gravidarum and with their severity, the whole group of pregnant women and the multiparae group showed significant differences in scores on emotion of Skindex-29 between the presence and absence of striae gravidarum (p = 0.012 and p = 0.011). Pregnant women with severe striae gravidarum showed significantly higher scores on emotion of Skindex-29 compared with those with absent or mild striae gravidarum (p < 0.001 and p = 0.005).ConclusionsThere was no difference in generic QOL of pregnant women between the presence and absence of striae gravidarum, although the occurrence and severity of striae gravidarum influenced their dermatology-specific QOL. Multiparae women were especially impaired by striae gravidarum and it is considered important to prevent or reduce the severity of striae gravidarum of the multiparae group.

Uterus allotransplantation in cynomolgus macaque: A preliminary experience with non‐human primate models

Uterine transplantation (UTx) is a potential option for child‐bearing in women with uterine infertility. Recovery of uterine function after allogeneic UTx in non‐human primates has not been reported. The objective of this study is to establish the functional uterine transplant model in non‐human primates.

Risks for Donors in Uterus Transplantation

Uterus transplantation (UTx) is an alternative to gestational surrogacy and adoption for patients with absolute uterine infertility. Studies have been conducted in animals, and UTx is now within the reach of clinical application in humans. Procedures in humans have been published, but many medical, ethical, and social problems and risks of UTx require discussion prior to widespread clinical application, from the perspectives of donors, recipients, families, and newborns. In this article, we summarize the burdens and risks of UTx, with a focus on donors who provide the uterus.

Uterine transplantation in primates: A mini-review of the literature

Assisted reproductive technology has improved markedly in recent years, and many infertile patients have had children with the use of this technology. However, women with infertility due to an absent or nonfunctional uterus currently have no option of having a genetically linked child other than gestational surrogacy. Uterus transplantation (UTx) is now a possible approach for women with uterine-factor infertility to deliver a child. UTx studies have been performed in many animals, and accumulation of data from these studies has brought UTx within reach of clinical application. This has led to performance of UTx in humans in Saudi Arabia, Turkey, and Sweden. However, there has yet to be a delivery after allogeneic UTx in primates. More basic studies in primates are needed, and data from research in primates can provide important information for establishment of UTx in humans. In this review, we summarize the literature on UTx studies, with a focus on primates, both human and nonhuman.

Prevention of striae gravidarum and quality of life among pregnant Japanese women.

BACKGROUND striae gravidarum affects the quality of life (QOL) of Japanese pregnant women. Many pregnant women use skin moisturisers to prevent striae gravidarum. However, the relationship between these preventive steps and QOL remains unclear. OBJECTIVE to evaluate the moisturising effect and QOL of pregnant women in an urban prefecture in central Japan with preventive steps against striae gravidarum. DESIGN AND METHOD cross-sectional study. Pregnant women at 36 weeks of gestation were recruited at antenatal examinations. SETTING four private clinics in an urban prefecture in central Japan. PARTICIPANTS 156 pregnant women consisting of 83 primiparae and 73 multiparae were analysed. MEASUREMENTS a self-administered questionnaire, the severity of striae gravidarum assessed by Daveys score and the dermatology-specific QOL were assessed by Skindex29. The water content in the stratum corneum of each womans abdomen was measured with a Moisture checker. The Ethical Committee of Osaka University Medical School approved the study. FINDINGS the prevalence of striae gravidarum was 37.8% and 121 (77.6%), including 76 (91.6%) primiparae and 45 (61.6%) multiparae, said they used a cream and/or lotion in an attempt to prevent striae gravidarum. The water content in the stratum corneum of the abdominal wall increased significantly after using cream and/or lotion (p=0.001). The severity and presence of striae gravidarum were not correlated with the preventive steps or water content in the stratum corneum of the abdominal wall (p=0.330 and p=0.835). Pregnant women who took the preventive steps showed higher scores for emotion on Skindex29 than those who did not (p=0.002). Although pregnant women with striae gravidarum showed a lower QOL for emotion than those without striae gravidarum (p=0.045), those who took the preventive steps maintained a similar level of QOL for emotion regardless of striae gravidarum. There have been few trials evaluating the QOL of pregnant women with striae gravidarum so a comparison of results among studies and determination of an appropriate sample size could not be conducted. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE preventive steps increase the amount of water content in the stratum corneum but this does not prevent striae gravidarum. Although pregnant women with striae gravidarum showed a lower QOL for emotion, the preventive steps were correlated with the level of QOL for emotion in pregnant women with striae gravidarum. Midwives need to absorb such information and recommend moisturising skin care for pregnant women.

Uterine Transplantation: Towards Clinical Application

1 Ozkan O, Erman Akar M, Ozkan O, Erdogan O, Hadimioglu N, Yilmaz M, Gunseren F, Cincik M, Pestereli E, Kocak H, Mutlu D, Dinckan A, Gecici O, Bektas G, Suleymanlar G: Preliminary results of the first human uterus transplantation from a multiorgan donor. Fertil Steril 2013; 99: 470–476.e5. 2 Fageeh W, Raffa H, Jabbad H, Marzouki A: Transplantation of the human uterus. Int J Gynaecol Obstet 2002; 76: 245–251. 3 Milliez J: Uterine transplantation FIGO Committee for the Ethical Aspects of Human Reproduction and Women’s Health. Int J Gynaecol Obstet 2009; 106: 270. 4 Hansen A: Swedish surgeons report world’s first uterus transplantation from mother to daughter. BMJ 2012; 345:e6357. Letter to the Editor

Identification of mature plasma cells in early rat yolk sac. A possible origin from the endodermal cell layer: Immunohistochemistry and immunoelectron microscopic study

Plasma cells play a pivotal role in the immune system and are responsible for the synthesis and release of immunoglobulins. Numerous in vitro culture experiments on the yolk sac demonstrated the generation of mature cells of the myeloid and lymphoid lineages under appropriate culture conditions. However, there are no reports describing the development of mature lymphoid cells in the yolk sac so far. For this reason, we undertook this study to investigate the development of antibody‐containing plasma cells during early yolk sac haematopoiesis. Immunohistochemistry and immunoelectron microscopy were employed in the study. Results of this work demonstrated very weak immune staining for the intracytoplasmic IgA, IgG, and IgM at days 10 and 11 of embryonic life, while dark staining was obtained at 12 days. Positive staining was localized to the endodermal cell layer. Electron microscopic examinations revealed the existence of cells with the typical characteristics of plasma cells inside the endodermal cell layer, which may suggest their endodermal origin. To further verify the nature of these cells, intracytoplasmic immunoglobulins were demonstrated by immunoelectron microscopy. The present study demonstrated emergence of mature functioning plasma cells in early rat yolk sac. In a previous work we hypothesized the possibility of endodermal origin of yolk sac macrophages. This study adds additional evidence to support that hypothesis. The possible role of plasma cells in the yolk sac is discussed.

Daily walking is effective for the management of pregnant women with gestational diabetes mellitus

This study evaluated the usefulness of daily walking for gestational diabetes mellitus (GDM) management by analyzing the relationship between daily walking and glucose tolerance in pregnant women with GDM who were in the second trimester.